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Vol. 87, No. 1, 2011
Issue release date: August 2011
Section title: Original Paper
Editor's Choice -- Free Access
Urol Int 2011;87:42–48
(DOI:10.1159/000325463)

Concomitant Carcinoma in situ in Cystectomy Specimens Is Not Associated with Clinical Outcomes after Surgery

Nuhn P.a · Bastian P.J.a, b · Novara G.c · Svatek R.S.d · Karakiewicz P.I.e · Skinner E.f · Fradet Y.g · Izawa J.I.h · Kassouf W.i · Montorsi F.j · Müller S.C.b · Fritsche H.-M.k · Sonpavde G.l · Tilki D.a · Isbarn H.d · Ficarra V.j · Dinney C.P.d · Shariat S.F.m
aLudwig-Maximilians-Universität München, Munich, bUniversität Bonn, Bonn, Germany; cUniversity of Padua, Padua, Italy; dUniversity of Texas MD Anderson Cancer Center, Houston, Tex., USA; eUniversity of Montréal, Montréal, Qué., Canada; fUniversity of Southern California, Los Angeles, Calif., USA; gLaval University, Québec City, Qué., hUniversity of Western Ontario, London, Ont., iMcGill University Health Center, Montréal, Qué., Canada; jVita Salute, Milano, Italy; kCaritas St. Josef Medical Center, Universität Regensburg, Regensburg, Germany; lBaylor College of Medicine, Houston, Tex., mWeill Cornell Medical College, New York, N.Y., USA
email Corresponding Author

Abstract

Objective: The aim of this study was to externally validate the prognostic value of concomitant urothelial carcinoma in situ (CIS) in radical cystectomy (RC) specimens using a large international cohort of bladder cancer patients. Methods: The records of 3,973 patients treated with RC and bilateral lymphadenectomy for urothelial carcinoma of the bladder (UCB) at nine centers worldwide were reviewed. Surgical specimens were evaluated by a genitourinary pathologist at each center. Uni- and multivariable Cox regression models addressed time to recurrence and cancer-specific mortality after RC. Results: 1,741 (43.8%) patients had concomitant CIS in their RC specimens. Concomitant CIS was more common in organ-confined UCB and was associated with lymphovascular invasion (p < 0.001). Concomitant CIS was not associated with either disease recurrence or cancer-specific death regardless of pathologic stage. The presence of concomitant CIS did not improve the predictive accuracy of standard predictors for either disease recurrence or cancer-specific death in any of the subgroups. Conclusions: We could not confirm the prognostic value of concomitant CIS in RC specimens. This, together with the discrepancy between pathologists in determining the presence of concomitant CIS at the morphologic level, limits the clinical utility of concomitant CIS in RC specimens for clinical decision-making.

© 2011 S. Karger AG, Basel


  

Key Words

  • Carcinoma in situ
  • Radical cystectomy, prognosis
  • Bladder cancer
  • Urothelial carcinoma, survival

References

  1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ: Cancer statistics, 2009. CA Cancer J Clin 2009;59:225–249.
  2. Skinner DG, Richie JP, Cooper PH, Waisman J, Kaufman JJ: The clinical significance of carcinoma in situ of the bladder and its association with overt carcinoma. J Urol 1974;112:68–71.
  3. Utz DC, Hanash KA, Farrow GM: The plight of the patient with carcinoma in situ of the bladder. J Urol 1970;103:160–164.
  4. Lamm DL: Carcinoma in situ. Urol Clin North Am 1992;19:499–508.
  5. Shariat SF, Palapattu GS, Karakiewicz PI, Rogers CG, Vazina A, Bastian PJ, et al: Concomitant carcinoma in situ is a feature of aggressive disease in patients with organ-confined TCC at radical cystectomy. Eur Urol 2007;51:152–160.

    External Resources

  6. Shariat SF, Palapattu GS, Amiel GE, Karakiewicz PI, Rogers CG, Vazina A, et al: Characteristics and outcomes of patients with carcinoma in situ only at radical cystectomy. Urology 2006;68:538–542.

    External Resources

  7. Gupta A, Lotan Y, Bastian PJ, Palapattu GS, Karakiewicz PI, Raj GV, et al: Outcomes of patients with clinical T1 grade 3 urothelial cell bladder carcinoma treated with radical cystectomy. Urology 2008;71:302–307.

    External Resources

  8. Zincke H, Garbeff PJ, Beahrs JR: Upper urinary tract transitional cell cancer after radical cystectomy for bladder cancer. J Urol 1984;131:50–52.
  9. Solsona E, Iborra I, Ricos JV, Dumont R, Casanova JL, Calabuig C: Upper urinary tract involvement in patients with bladder carcinoma in situ (Tis): its impact on management. Urology 1997;49:347–352.
  10. Millan-Rodriguez F, Chechile-Toniolo G, Salvador-Bayarri J, Huguet-Perez J, Vicente-Rodriguez J: Upper urinary tract tumors after primary superficial bladder tumors: prognostic factors and risk groups. J Urol 2000;164:1183–1187.
  11. Nixon RG, Chang SS, Lafleur BJ, Smith JJ, Cookson MS: Carcinoma in situ and tumor multifocality predict the risk of prostatic urethral involvement at radical cystectomy in men with transitional cell carcinoma of the bladder. J Urol 2002;167:502–505.
  12. Kattan MW: Judging new markers by their ability to improve predictive accuracy. J Natl Cancer Inst 2003;95:634–635.
  13. Shariat SF, Karakiewicz PI, Ashfaq R, Lerner SP, Palapattu GS, Cote RJ, et al: Multiple biomarkers improve prediction of bladder cancer recurrence and mortality in patients undergoing cystectomy. Cancer 2008;112:315–325.
  14. Fine JP: Regression modeling of competing crude failure probabilities. Biostatistics 2001;2:85–97.

    External Resources

  15. Harrell FE Jr, Califf RM, Pryor DB, Lee KL, Rosati RA: Evaluating the yield of medical tests. JAMA 1982;247:2543–2546.
  16. Harrell FE Jr, Lee KL, Mark DB: Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med 1996;15:361–387.
  17. Habuchi T, Ogawa O, Kakehi Y, Ogura K, Koshiba M, Sugiyama T, et al: Allelic loss of chromosome 17p in urothelial cancer: strong association with invasive phenotype. J Urol 1992;148:1595–1599.
  18. Spruck CH 3rd, Ohneseit PF, Gonzalez-Zulueta M, Esrig D, Miyao N, Tsai YC, et al: Two molecular pathways to transitional cell carcinoma of the bladder. Cancer Res 1994;54:784–788.
  19. Rosin MP, Cairns P, Epstein JI, Schoenberg MP, Sidransky D: Partial allelotype of carcinoma in situ of the human bladder. Cancer Res 1995;55:5213–5216.
  20. Knowles MA, Elder PA, Williamson M, Cairns JP, Shaw ME, Law MG: Allelotype of human bladder cancer. Cancer Res 1994;54:531–538.
  21. Dyrskjot L, Kruhoffer M, Thykjaer T, Marcussen N, Jensen JL, Moller K, et al: Gene expression in the urinary bladder: a common carcinoma in situ gene expression signature exists disregarding histopathological classification. Cancer Res 2004;64:4040–4048.
  22. Sarkis AS, Dalbagni G, Cordon-Cardo C, Melamed J, Zhang ZF, Sheinfeld J, et al: Association of p53 nuclear overexpression and tumor progression in carcinoma in situ of the bladder. J Urol 1994;152:388–392.
  23. Shariat SF, Pahlavan S, Baseman AG, Brown RM, Green AE, Wheeler TM, et al: E-cadherin expression predicts clinical outcome in carcinoma in situ of the urinary bladder. Urology 2001;57:60–65.
  24. Shariat SF, Kim JH, Ayala GE, Kho K, Wheeler TM, Lerner SP: Cyclooxygenase-2 is highly expressed in carcinoma in situ and T1 transitional cell carcinoma of the bladder. J Urol 2003;169:938–942.
  25. Shariat SF, Kim J, Raptidis G, Ayala GE, Lerner SP: Association of p53 and p21 expression with clinical outcome in patients with carcinoma in situ of the urinary bladder. Urology 2003;61:1140–1155.
  26. Masood S, Sriprasad S, Palmer JH, Mufti GR: T1G3 bladder cancer – indications for early cystectomy. Int Urol Nephrol 2004;36:41–44.
  27. Vicente J, Laguna MP, Duarte D, Algaba F, Chechile G: Carcinoma in situ as a prognostic factor for G3pT1 bladder tumours. Br J Urol 1991;68:380–382.
  28. Smits G, Schaafsma E, Kiemeney L, Caris C, Debruyne F, Witjes JA: Microstaging of pT1 transitional cell carcinoma of the bladder: identification of subgroups with distinct risks of progression. Urology 1998;52:1009–1013.
  29. Orsola A, Trias I, Raventos CX, Espanol I, Cecchini L, Bucar S, et al: Initial high-grade T1 urothelial cell carcinoma: feasibility and prognostic significance of lamina propria invasion microstaging (T1a/b/c) in BCG-treated and BCG-non-treated patients. Eur Urol 2005;48:231–238.
  30. Sylvester RJ, van der Meijden AP, Oosterlinck W, Witjes JA, Bouffioux C, Denis L, et al: Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2,596 patients from seven EORTC trials. Eur Urol 2006;49:466–465.

  

Author Contacts

Shahrokh F. Shariat, MD, PhD
Department of Urology and Medical Oncology
Brady Urologic Health Center, Weill Cornell Medical College
525 East 68th Street, Starr 900, New York, NY 10065 (USA)
Tel. +1 212 746 5562, E-Mail sfshariat@gmail.com

  

Article Information

Received: December 1, 2010
Accepted after revision: February 14, 2011
Published online: June 9, 2011
Number of Print Pages : 7
Number of Figures : 0, Number of Tables : 3, Number of References : 30

  

Publication Details

Urologia Internationalis

Vol. 87, No. 1, Year 2011 (Cover Date: August 2011)

Journal Editor: Wirth M.P. (Dresden), Porena M. (Perugia), Hakenberg O.W. (Rostock), Castro-Diaz D. (Santa Cruz de Tenerife)
ISSN: 0042-1138 (Print), eISSN: 1423-0399 (Online)

For additional information: http://www.karger.com/UIN


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Objective: The aim of this study was to externally validate the prognostic value of concomitant urothelial carcinoma in situ (CIS) in radical cystectomy (RC) specimens using a large international cohort of bladder cancer patients. Methods: The records of 3,973 patients treated with RC and bilateral lymphadenectomy for urothelial carcinoma of the bladder (UCB) at nine centers worldwide were reviewed. Surgical specimens were evaluated by a genitourinary pathologist at each center. Uni- and multivariable Cox regression models addressed time to recurrence and cancer-specific mortality after RC. Results: 1,741 (43.8%) patients had concomitant CIS in their RC specimens. Concomitant CIS was more common in organ-confined UCB and was associated with lymphovascular invasion (p < 0.001). Concomitant CIS was not associated with either disease recurrence or cancer-specific death regardless of pathologic stage. The presence of concomitant CIS did not improve the predictive accuracy of standard predictors for either disease recurrence or cancer-specific death in any of the subgroups. Conclusions: We could not confirm the prognostic value of concomitant CIS in RC specimens. This, together with the discrepancy between pathologists in determining the presence of concomitant CIS at the morphologic level, limits the clinical utility of concomitant CIS in RC specimens for clinical decision-making.

© 2011 S. Karger AG, Basel


  

Author Contacts

Shahrokh F. Shariat, MD, PhD
Department of Urology and Medical Oncology
Brady Urologic Health Center, Weill Cornell Medical College
525 East 68th Street, Starr 900, New York, NY 10065 (USA)
Tel. +1 212 746 5562, E-Mail sfshariat@gmail.com

  

Article Information

Received: December 1, 2010
Accepted after revision: February 14, 2011
Published online: June 9, 2011
Number of Print Pages : 7
Number of Figures : 0, Number of Tables : 3, Number of References : 30

  

Publication Details

Urologia Internationalis

Vol. 87, No. 1, Year 2011 (Cover Date: August 2011)

Journal Editor: Wirth M.P. (Dresden), Porena M. (Perugia), Hakenberg O.W. (Rostock), Castro-Diaz D. (Santa Cruz de Tenerife)
ISSN: 0042-1138 (Print), eISSN: 1423-0399 (Online)

For additional information: http://www.karger.com/UIN


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 12/1/2010
Accepted: 2/14/2011
Published online: 6/9/2011
Issue release date: August 2011

Number of Print Pages: 7
Number of Figures: 0
Number of Tables: 3

ISSN: 0042-1138 (Print)
eISSN: 1423-0399 (Online)

For additional information: http://www.karger.com/UIN


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ: Cancer statistics, 2009. CA Cancer J Clin 2009;59:225–249.
  2. Skinner DG, Richie JP, Cooper PH, Waisman J, Kaufman JJ: The clinical significance of carcinoma in situ of the bladder and its association with overt carcinoma. J Urol 1974;112:68–71.
  3. Utz DC, Hanash KA, Farrow GM: The plight of the patient with carcinoma in situ of the bladder. J Urol 1970;103:160–164.
  4. Lamm DL: Carcinoma in situ. Urol Clin North Am 1992;19:499–508.
  5. Shariat SF, Palapattu GS, Karakiewicz PI, Rogers CG, Vazina A, Bastian PJ, et al: Concomitant carcinoma in situ is a feature of aggressive disease in patients with organ-confined TCC at radical cystectomy. Eur Urol 2007;51:152–160.

    External Resources

  6. Shariat SF, Palapattu GS, Amiel GE, Karakiewicz PI, Rogers CG, Vazina A, et al: Characteristics and outcomes of patients with carcinoma in situ only at radical cystectomy. Urology 2006;68:538–542.

    External Resources

  7. Gupta A, Lotan Y, Bastian PJ, Palapattu GS, Karakiewicz PI, Raj GV, et al: Outcomes of patients with clinical T1 grade 3 urothelial cell bladder carcinoma treated with radical cystectomy. Urology 2008;71:302–307.

    External Resources

  8. Zincke H, Garbeff PJ, Beahrs JR: Upper urinary tract transitional cell cancer after radical cystectomy for bladder cancer. J Urol 1984;131:50–52.
  9. Solsona E, Iborra I, Ricos JV, Dumont R, Casanova JL, Calabuig C: Upper urinary tract involvement in patients with bladder carcinoma in situ (Tis): its impact on management. Urology 1997;49:347–352.
  10. Millan-Rodriguez F, Chechile-Toniolo G, Salvador-Bayarri J, Huguet-Perez J, Vicente-Rodriguez J: Upper urinary tract tumors after primary superficial bladder tumors: prognostic factors and risk groups. J Urol 2000;164:1183–1187.
  11. Nixon RG, Chang SS, Lafleur BJ, Smith JJ, Cookson MS: Carcinoma in situ and tumor multifocality predict the risk of prostatic urethral involvement at radical cystectomy in men with transitional cell carcinoma of the bladder. J Urol 2002;167:502–505.
  12. Kattan MW: Judging new markers by their ability to improve predictive accuracy. J Natl Cancer Inst 2003;95:634–635.
  13. Shariat SF, Karakiewicz PI, Ashfaq R, Lerner SP, Palapattu GS, Cote RJ, et al: Multiple biomarkers improve prediction of bladder cancer recurrence and mortality in patients undergoing cystectomy. Cancer 2008;112:315–325.
  14. Fine JP: Regression modeling of competing crude failure probabilities. Biostatistics 2001;2:85–97.

    External Resources

  15. Harrell FE Jr, Califf RM, Pryor DB, Lee KL, Rosati RA: Evaluating the yield of medical tests. JAMA 1982;247:2543–2546.
  16. Harrell FE Jr, Lee KL, Mark DB: Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med 1996;15:361–387.
  17. Habuchi T, Ogawa O, Kakehi Y, Ogura K, Koshiba M, Sugiyama T, et al: Allelic loss of chromosome 17p in urothelial cancer: strong association with invasive phenotype. J Urol 1992;148:1595–1599.
  18. Spruck CH 3rd, Ohneseit PF, Gonzalez-Zulueta M, Esrig D, Miyao N, Tsai YC, et al: Two molecular pathways to transitional cell carcinoma of the bladder. Cancer Res 1994;54:784–788.
  19. Rosin MP, Cairns P, Epstein JI, Schoenberg MP, Sidransky D: Partial allelotype of carcinoma in situ of the human bladder. Cancer Res 1995;55:5213–5216.
  20. Knowles MA, Elder PA, Williamson M, Cairns JP, Shaw ME, Law MG: Allelotype of human bladder cancer. Cancer Res 1994;54:531–538.
  21. Dyrskjot L, Kruhoffer M, Thykjaer T, Marcussen N, Jensen JL, Moller K, et al: Gene expression in the urinary bladder: a common carcinoma in situ gene expression signature exists disregarding histopathological classification. Cancer Res 2004;64:4040–4048.
  22. Sarkis AS, Dalbagni G, Cordon-Cardo C, Melamed J, Zhang ZF, Sheinfeld J, et al: Association of p53 nuclear overexpression and tumor progression in carcinoma in situ of the bladder. J Urol 1994;152:388–392.
  23. Shariat SF, Pahlavan S, Baseman AG, Brown RM, Green AE, Wheeler TM, et al: E-cadherin expression predicts clinical outcome in carcinoma in situ of the urinary bladder. Urology 2001;57:60–65.
  24. Shariat SF, Kim JH, Ayala GE, Kho K, Wheeler TM, Lerner SP: Cyclooxygenase-2 is highly expressed in carcinoma in situ and T1 transitional cell carcinoma of the bladder. J Urol 2003;169:938–942.
  25. Shariat SF, Kim J, Raptidis G, Ayala GE, Lerner SP: Association of p53 and p21 expression with clinical outcome in patients with carcinoma in situ of the urinary bladder. Urology 2003;61:1140–1155.
  26. Masood S, Sriprasad S, Palmer JH, Mufti GR: T1G3 bladder cancer – indications for early cystectomy. Int Urol Nephrol 2004;36:41–44.
  27. Vicente J, Laguna MP, Duarte D, Algaba F, Chechile G: Carcinoma in situ as a prognostic factor for G3pT1 bladder tumours. Br J Urol 1991;68:380–382.
  28. Smits G, Schaafsma E, Kiemeney L, Caris C, Debruyne F, Witjes JA: Microstaging of pT1 transitional cell carcinoma of the bladder: identification of subgroups with distinct risks of progression. Urology 1998;52:1009–1013.
  29. Orsola A, Trias I, Raventos CX, Espanol I, Cecchini L, Bucar S, et al: Initial high-grade T1 urothelial cell carcinoma: feasibility and prognostic significance of lamina propria invasion microstaging (T1a/b/c) in BCG-treated and BCG-non-treated patients. Eur Urol 2005;48:231–238.
  30. Sylvester RJ, van der Meijden AP, Oosterlinck W, Witjes JA, Bouffioux C, Denis L, et al: Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2,596 patients from seven EORTC trials. Eur Urol 2006;49:466–465.